Targeted Isolation of Antibodies Directed against Major Sites of SIV Env Vulnerability

PLoS Pathogens

Zizhang Sheng¹  Lawrence Shapiro¹  George M. Shaw²  Hui Li²  Richard Wyatt³  Bimal K. Chakrabarti⁴  Carole A. Bewley⁵  Sabrina Lusvarghi⁵  Cameron Adams⁶  Peter D. Kwong⁶  Richard Nguyen⁶  Tongqing Zhou⁶  Hugh C. Welles⁶  Rosemarie D. Mason⁶  John R. Mascola⁶  Sijy O’Dell⁶  Jason Gorman⁶  Mario Roederer⁶ 

[1] Department of Biochemistry and Molecular Biophysics and Department of Systems Biology, Columbia University, New York, New York, United States of America;Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America;IAVI Neutralizing Antibody Center, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America;International AIDS Vaccine Initiative (IAVI) HIV Vaccine Design Program, Translational Health Science and Technology Institute, Haryana, India;Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, United States of America;Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States of America

关键词: SIV;    B cells;    HIV-1;    Antibodies;    Cell binding;    Macaque;    Rhesus monkeys;    Cell staining;   

DOI  :  10.1371/journal.ppat.1005537

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The simian immunodeficiency virus (SIV) challenge model of lentiviral infection is often used as a model to human immunodeficiency virus type 1 (HIV-1) for studying vaccine mediated and immune correlates of protection. However, knowledge of the structure of the SIV envelope (Env) glycoprotein is limited, as is knowledge of binding specificity, function and potential efficacy of SIV antibody responses. In this study we describe the use of a competitive probe binding sort strategy as well as scaffolded probes for targeted isolation of SIV Env-specific monoclonal antibodies (mAbs). We isolated nearly 70 SIV-specific mAbs directed against major sites of SIV Env vulnerability analogous to broadly neutralizing antibody (bnAb) targets of HIV-1, namely, the CD4 binding site (CD4bs), CD4-induced (CD4i)-site, peptide epitopes in variable loops 1, 2 and 3 (V1, V2, V3) and potentially glycan targets of SIV Env. The range of SIV mAbs isolated includes those exhibiting varying degrees of neutralization breadth and potency as well as others that demonstrated binding but not neutralization. Several SIV mAbs displayed broad and potent neutralization of a diverse panel of 20 SIV viral isolates with some also neutralizing HIV-27312A. This extensive panel of SIV mAbs will facilitate more effective use of the SIV non-human primate (NHP) model for understanding the variables in development of a HIV vaccine or immunotherapy.

【 授权许可】

CC BY